PlagMab: Therapeutic monoclonal antibodies against Plague (Yersinia pestis)
Yersinia pestis, agent of plague, has a deadly power well known after three major historical pandemics that have devastated human populations. Plague is still present in rodents in large endemic areas and human cases are recorded every year in Africa, Asia and America. The possibility that the pathogen be used as a bioterrorism agent to cause plague in civilian and military populations is also a serious threat. Although an effort towards vaccination is ongoing, no efficient and safe vaccine is currently available.
Although antibiotics are effective to treat plague, resistance (mono and multidrug resistance) has recently been observed in Madagascar on strains of Y. pestis, conferred by a self-transferable plasmid, which has been detected in many enterobacteria worldwide. In the absence of an approved vaccine against plague, and as an alternative to antibiotics, we wish notably to develop monoclonal antibodies for therapeutic use as recently described for viral diseases. This strategy is made possible since several animal works have demonstrated the protective role of antibodies against Y. pestis infection and since the bacillus exhibits a very limited genetic variability due to its recent emergence.
The Yersinia Unit at Institut Pasteur Paris (IPP) and in collaboration with the Plague Unit and Immunology Unit at the Institut Pasteur Madagascar (IPM) are partners in this project. Specifically, we will analyze the B cell immune responses against short peptides covering Y. pestis proteins known to be important either for their immunogenicity or for their pathogenicity. Such a fine mapping has never been performed before for Y. pestis. This project will lead to the identification of the major B epitopes of Y. pestis key antigens, their correlation with a protective humoral immunity, and notably allow to derive from B cells of patients identified with protective antibodies the development of monoclonal antibodies suitable for therapeutic use.
Speaker: Hebert Echenique Rivera, Ph.D.
Peruvian – French scientist. Bachelor Degree in Biology at Universidad Nacional de San Agustin (Arequipa – Peru). Training in bacterial genetics at University of Palermo (Palermo – Italy) for one year and Ph.D. in Evolutionary Biology (section Cellular and Molecular Biology) at University of Siena (Siena – Italy) in the joint Ph.D. program Novartis Vaccines – University of Siena (Siena – Italy). Post Doctoral Training at the Paris Cardiovascular Research Center (Marie Curie European Fellow) working on mechanisms of host – pathogen interactions of Neisseria meningitidis . In 2018 joined the Yersinia Research Unit at Institut Pasteur of Paris as post doctoral researcher. The main topics of research has been the study of host – pathogen interactions of different human pathogens such Neisseria meningitidis, Yersinia enterocolitica and Yersinia pestis. Since 2022 Dr. Echenique Rivera is involved in the project for the development of monoclonal antibodies against Yersinia pestis for therapeutic purposes in collaboration with the Institut Pasteur of Madasgascar (Plague Unit and Immunology Unit).
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